与阿片成瘾相关分子互作网络的构建及生物学通路预测

Construction of molecular interaction network and the prediction of pathways underlying opioid addiction

目的:探索与阿片成瘾相关的分子互作关系及遗传因素在阿片类药物成瘾过程中的角色。方法:提取与阿片成瘾相关的基因构建分子互作网络,寻找在成瘾过程中起关键作用的hub结点,将其映射到代谢通路上,筛选出与成瘾相关的具有生物学和统计学意义的通路,并以此为依据从整体上预测并构建了与阿片成瘾相关的生物学通路网络。结果:构建了与阿片成瘾相关的分子互作网络,找出了一些在网络中可能与成瘾发生过程密切相关的包括已知阿片类受体在内的46个hub结点及其关联蛋白,代谢通路中的成瘾相关的调控组分等。另外还挖掘出与阿片成瘾相关的包含多个信号转导通路在内的20个生物学通路,进而构建了通路网络并找出其中的共有模块,为进一步挖掘与成瘾相关的信号转导信息提供依据。结论:阿片成瘾过程是多种遗传因子在多水平上共同发生适应性变化引起的一种综合效应,并涉及了多个代谢及信号通路。

AIM： To explore the interactions of molecules underlying opioid addiction and find out the roles that the genetic factors play in the course of opioid addiction. METHODS： We have downloaded several addiction related gene data and constructed an addiction related molecular interaction network. In addition, we found out the important hubs which could play essential roles in addiction, and screened the pathways that were statistically significantly enriched. On the base of that, we connected those pathways into a molecular interaction pathway network. RESULTS： We constructed an addiction related compound network and also found 46 important hubs of the network, proteins which had the interconnection function in the addiction process, and the addiction related regulation parts in the metabolism pathways. Moreover, we obtained 20 addiction related pathways and predicted an addiction related pathway network at a global level. CONCLUSION： Opioid addiction process is a kind of comprehensive effect caused by the common adaptability changes of multiple genetic factors, involving many metabolisms and signal pathways.